The NIH is uniquely suited to create a rare CNS cancer initiative, particularly with the support provided by the Moonshot Initiative. This effort utilizes the following specific resources of the NIH. This has required developing a clinical trial infrastructure, including data management system, to oversee the disease specific therapeutic and natural history studies. Collaborations with experts in imaging technologies to create imaging biomarkers and routine imaging for monitoring response to therapies are planned. A tissue repository has been established to store both tumor and normal tissue for molecular analyses including genomics, metabolomics, and proteomics with the intent of advancing the understanding of tumor biology and pathogenesis leading to better prognostic information, sub-classification and ultimately markers predictive of response to specific treatments. Additionally, specific testing capabilities have been developed such as the CNS Molecular Panel described above and additional tests are under development. For example, an immunotherapy trial is anticipated, and immunologic monitoring capabilities will be needed as a critical component of this study. NIH-based outreach efforts will be utilized to interact with patient advocacy groups to enhance patient participation in these efforts and provide a venue for educational programs to improve patient and caregiver understanding of their uncommon disease. Two clinical trials are recently open (17C0102 Immune Checkpoint Inhibitor Nivolumab in People With Select Rare CNS Cancers; and 15C0118 Phase II Trial of GI-6301 in Combination With Standard of Care Definitive Radiotherapy in Locally Advanced, Unresectable, Chordoma). Most recently, we have established the NCI-CONNECT: Comprehensive Oncology Network Evaluating Rare CNS Tumors for fostering patient-advocacy-provider partnerships and networks to improve approaches to care and treatment.